Mechanistic insights into Zika virus NS3 helicase inhibition by Epigallocatechin-3-gallate: Supplementary Files

Deepak Kumar; Nitin Sharma; Murali Aarthy; Sanjeev Singh; Rajanish Giri

In ZIKV NS3 helicase the RNA binding site along with NTPase site has flexible pockets containing critical loop regions needed to perform function (21, 22) . Therefore, we also studied the possibility of EGCG interacting at RNA binding site. This was due to the fact that polyphenols have shown potential interactions with intrinsically disordered regions in proteins and could be seen as novel strategies of drug development against IDPs (38) . Also, literature has shown that viral proteins have several short stretches of disordered regions within proteins and more propensity of intrinsically disordered active sites (22, 24, 39) . Our docking and MD simulations studies are showing that EGCG has the ability to bind at the entry site of RNA binding pocket with significant interactions. More specifically, EGCG is showing different types of interactions (H-bond, ionic, salt bridge) with residues GLU 413, MET 414, LYS 431, PHE289 and ASP 410. In crystal structure, these residues are playing key role in binding to RNA (21) . In our MD simulations, it has also reported that EGCG binding at NTPase site is increasing fluctuations in RNA site which could interpreted as an allosteric relationship between two sites. This observation could be supported by the recent study on DENV helicase where NTPase and RNA sites show allosteric effects.